Pain medicines work in different ways to help relieve pain. Doctors and pharmacists can recommend different types of medication depending on the source of pain and other factors.
Choosing the most appropriate medication requires matching the cause of pain with the best medication that targets it. Some people may experience side effects, but the severity can vary greatly.
While over-the-counter (OTC) pain medications are available, stronger ones — for example, opioids — require a doctor’s prescription and monitoring.
This article provides an overview of how pain medicines work.
Experts are still unsureTrusted Source how acetaminophen works to treat or relieve pain. One theory is that acetaminophen attaches itself to a variation of an enzyme (a type of protein) involved in pain known as cyclooxygenase-3 (COX-3).
However, researchers have yet to confirmTrusted Source this theory in humans.
If acetaminophen blocks COX-3, it will stop the pathway that leads to prostaglandin production in the central nervous system. Prostaglandins are natural chemicals the body produces that have associations with pain and inflammation. Therefore, blocking COX-3 provides pain relief.
How long does it take to work?
How long it takes acetaminophen to work depends on the formTrusted Source. The table below details the different forms of the medication and how long they can take to start working.
| Form of acetaminophen | Onset of action |
| Intravenous (via injection) | 5–10 minutes |
| Oral (tablet, capsule, syrup, solution, suspension) | Less than 1 hour |
| Rectal (suppository) | 35–45 minutesTrusted Source |
Possible side effects
Acetaminophen is a safe medication that people can find over the counter.
Possible side effectsTrusted Source include:
- rash
- allergic reaction
- disturbance in blood cell count — for example, low red blood cell count
- electrolyte imbalances — for example, low sodium levels in the blood
- kidney failure
Different side effects may occur with intravenous (IV) acetaminophen injections. These include:
- nausea
- vomiting
- abdominal pain
Nonsteroidal anti-inflammatory drugs (NSAIDs) block cyclooxygenase, which is an enzyme involved in producing prostaglandins. By blocking their production and release in the body, NSAIDs treat pain resulting from inflammation.
How long do they take to work?
NSAIDs come in various forms. These include oral capsules, tablets, suspensions, rectal suppositories, and IV injections.
Diclofenac is a specific type of NSAID in a topical form — meaning people apply it to the skin. This type can take 1–2 days to work.
IV injections of ibuprofen, for example, start working within secondsTrusted Source.
Oral forms will take the longest to work because they must travel through the digestive tract before being absorbed into the blood. Pain relief from oral ibuprofen can take about 30–60 minutes.
Possible side effects
OTC and prescription NSAIDs can cause side effects. These may occur in different body systems, such as the cardiovascular, digestive, and kidney systems. The possibleTrusted Source side effects of NSAIDs are:
- nausea
- upset stomach
- ulcers
- high blood pressure
- blood clots
- dizziness
- allergic reactions
Some NSAIDs are only available through a prescription because their side effects can be more severe in certain populations. For example, doctors may not recommend NSAIDs to people with a history of ulcers, stomach bleeding, or heart attack.
Opioids act on receptors (another type of protein) that are found in the nervous system and are involved in pain. Primarily, opioids act on “mu receptors” and activate them. In doing so, the medication blocks pain signals from reaching the central nervous system.
How long do they take to work?
Like other pain medicines, how long it takes opioids to work depends on the form. IV morphine, for example, acts the fastest. Within 5–10 minutesTrusted Source, a person can feel pain relief. Intramuscular injections take a little longer, between 10 and 30 minutes.
Oral opioids may take about 30 minutes before they start working.
Fentanyl is available in different forms that all have different onsets of action. The intranasal form (which a doctor administers through the nose) starts working within 5–10 minutes. The nebulizer form (which a person inhales) starts working immediately.
Possible side effects
Opioids have many side effects, which can limit their use. They can affect different body systems. These side effects include:
- feeling high
- feeling very tired
- constipation
- nausea
- vomiting
- allergic reaction
- slow heart rate
- trouble breathing
Overdose is a serious side effect of opioids, as it can have life threateningTrusted Source consequences.
Gabapentin (Gralise) and pregabalin (Lyrica) are two antiseizure medications that doctors prescribe for nerve pain. They reduce the release of proteins known as excitatory neurotransmitters in the central nervous system and which are typically involved in nerve pain.
How long do they take to work?
Gabapentin and pregabalin take days or weeksTrusted Source to start working. Doctors will adjust doses after about a week. If the person does not experience significant pain relief, the doctor will then increase the dose and readjust after another week.
Antiseizure medications take longer to start working than opioids, NSAIDs, and acetaminophen.
Possible side effects
The most commonTrusted Source side effects of pregabalin and gabapentin include:
- dizziness
- fluid buildup in the arms or legs
- feeling tired
The following table lists the possible side effects of these two antiseizure drugs:
| Side effects of pregabalin | Side effects of gabapentin |
| headache | uncontrolled muscle movements |
| nausea | confusion |
| weight gain | severe allergic reaction |
| feeling disoriented | suicidal thoughts or behaviors |
| blurry vision | depression |
| increased risk of suicidal thoughts | fever |
| bloating | infection |
| mood changes | Stevens-Johnson syndrome |
| respiratory problems | muscle disorder (rhabdomyolysis) |
Antidepressants such as amitriptyline (Elavil) and duloxetine (Cymbalta) also help relieve nerve pain. They work by acting on neurotransmitters known as serotonin and noradrenaline. These neurotransmitters play a role in determining the intensity of pain a person feels.
Blocking the effect of these neurotransmitters can help to suppress certain pain pathways in the brain. Also, these medications can act on other proteins and neurotransmitters that play a role in pain sensation.
How long do they take to work?
Like antiseizure medications, antidepressant pain relievers take weeks to start working. Doctors suggest waiting at least 6–8 weeksTrusted Source before considering that the medication is not working.
Possible side effects
TypicalTrusted Source side effects of antidepressant medications in treating pain include:
- nausea
- headache
- increased risk of suicidal thoughts
The following table lists some of the more specific side effects of duloxetine and amitriptyline.
| Side effects of duloxetine | Side effects of amitriptyline |
| feeling tired | changes in mental status |
| stomach pain | irregular heartbeat |
| increased blood pressure | dizziness |
| changes in body weight | increased sweating |
| reduced appetite | urinary retention |
| muscle pain or cramps | shaking |
| decreased libido | weight gain |
Local anesthetics are OTC products that people can apply to their skin. For example, an athlete may rub a local anesthetic on the skin near a sore muscle.
Lidocaine (Xylocaine) and capsaicin (Zostrix) creams are some examples of this medication type. They work by binding to sodium channels to block nerve cells in the body from sending pain signals to the brain.
How long do they take to work?
Local anesthetics such as these can act quickly to relieve muscle pain. This is because they are vasoactive, which means that the skin quickly absorbs them into the bloodstream.
Possible side effects
Lidocaine may cause local side effectsTrusted Source. These include:
- pain at the application area
- itchiness
- redness
- skin irritation
Capsaicin may also cause itchiness, a burning sensation on the skin, and rash.
Below are some common questions and answers on this topic:
Which one do doctors usually prescribe?
A 2018 studyTrusted Source listed the top 200 prescribed drugs in the United States. The top pain medicine was a drug combination of acetaminophen with hydrocodone, which is an opioid.
Other top pain relievers that doctors prescribe in the U.S. include the NSAIDs ibuprofen and meloxicam and the opioid oxycodone.
Which one is the strongest?
When a person uses them appropriately, opioids can provide the strongest pain relief. However, these pain medicines have the most side effects and risks. People can develop a tolerance and an addiction to opioids.
Doctors must follow up with people taking opioids for pain. They will monitor the response to pain and any potential for diversion.
What if pain medications are not working for someone?
When a person feels that a pain medication is not working as it should, it can be tempting to increase the dose. However, people should avoid doing this. Instead, they should only take medications as the label or their doctor advises.
If a medication is not working as expected or side effects become hard to manage, a person should speak with their healthcare professional.
Doctors and pharmacists can choose among different medications to treat pain.
The most effective pain medicines are those that act on the source of the pain. While opioids are the strongest pain relievers, an NSAID may be safer and more appropriate for pain resulting from inflammation.
Seeking medical attention when side effects become difficult to cope with or when pain medications are not working as they should is important.